Trial Outcomes & Findings for Comparing the Safety and Efficacy of BOL-303259-X Ophthalmic Solution With Timolol Maleate Ophthalmic Solution in Subjects With Open-Angle Glaucoma or Ocular Hypertension (NCT NCT01749930)

NCT ID: NCT01749930

Last Updated: 2018-11-21

Results Overview

Mean intraocular pressure (IOP) in the study eye measured at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 420 participants
• Primary outcome timeframe: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)
• Results posted on: 2018-11-21

Participant Flow

Participant milestones

Measure	BOL-303259-X BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye(s). BOL-303259-X: BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).	Timolol Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye(s). Timolol: Timolol will be administered BID once in the morning and once in the evening. BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).
Overall Study STARTED	283	137
Overall Study COMPLETED	253	125
Overall Study NOT COMPLETED	30	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparing the Safety and Efficacy of BOL-303259-X Ophthalmic Solution With Timolol Maleate Ophthalmic Solution in Subjects With Open-Angle Glaucoma or Ocular Hypertension

Baseline characteristics by cohort

Measure	BOL-303259-X n=278 Participants BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye(s). BOL-303259-X: BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).	Timolol n=136 Participants Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye(s). Timolol: Timolol will be administered BID once in the morning and once in the evening. BOL-303259-X: All participants will receive a topical ocular BOL-303259-X QD in the evening from 3 months (Visit 6) through 6 months (Visit7).	Total n=414 Participants Total of all reporting groups
Age, Continuous	65.0 years STANDARD_DEVIATION 9.77 • n=5 Participants	64.1 years STANDARD_DEVIATION 9.71 • n=7 Participants	64.7 years STANDARD_DEVIATION 9.75 • n=5 Participants
Sex: Female, Male Female	162 Participants n=5 Participants	79 Participants n=7 Participants	241 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants	57 Participants n=7 Participants	173 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=5 Participants	19 Participants n=7 Participants	55 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	242 Participants n=5 Participants	117 Participants n=7 Participants	359 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	69 Participants n=5 Participants	46 Participants n=7 Participants	115 Participants n=5 Participants
Race (NIH/OMB) White	204 Participants n=5 Participants	89 Participants n=7 Participants	293 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)

Population: Intent-to-treat population with LOCF

Mean intraocular pressure (IOP) in the study eye measured at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3).

Outcome measures

Measure	BOL-303259-X n=277 Participants BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye.	Timolol n=135 Participants Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye.	BOL-303259-X Safety Extension Phase Following completion of the efficacy phase, all subjects were converted to BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label safety extension phase
Mean IOP 8 am week 2	19.17 mm Hg Standard Deviation 3.748	19.61 mm Hg Standard Deviation 3.092	—
Mean IOP 12 pm week 2	18.46 mm Hg Standard Deviation 3.327	19.22 mm Hg Standard Deviation 3.241	—
Mean IOP 4 pm week 2	18.10 mm Hg Standard Deviation 3.135	18.79 mm Hg Standard Deviation 3.022	—
Mean IOP 8 am week 6	18.67 mm Hg Standard Deviation 3.272	19.59 mm Hg Standard Deviation 3.324	—
Mean IOP 12 pm week 6	18.02 mm Hg Standard Deviation 3.073	18.86 mm Hg Standard Deviation 3.169	—
Mean IOP 4 pm week 6	17.87 mm Hg Standard Deviation 3.114	18.85 mm Hg Standard Deviation 3.415	—
Mean IOP 8 am Month 3	18.68 mm Hg Standard Deviation 3.195	19.56 mm Hg Standard Deviation 3.318	—
Mean IOP 12 pm Month 3	17.92 mm Hg Standard Deviation 3.119	19.21 mm Hg Standard Deviation 3.129	—
Mean IOP 4 pm Month 3	17.72 mm Hg Standard Deviation 3.153	19.06 mm Hg Standard Deviation 3.002	—

SECONDARY outcome

Timeframe: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)

Population: Intent-to treat population with LOCF

Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months

Outcome measures

Measure	BOL-303259-X n=277 Participants BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye.	Timolol n=135 Participants Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye.	BOL-303259-X Safety Extension Phase Following completion of the efficacy phase, all subjects were converted to BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label safety extension phase
IOP ≤ 18 mm Hg	49 Participants	15 Participants	—

SECONDARY outcome

Timeframe: 8 AM, 12 PM, and 4 PM at Visit 4 (Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)

Population: Intent-to-treat population with LOCF

Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months

Outcome measures

Measure	BOL-303259-X n=277 Participants BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye.	Timolol n=135 Participants Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye.	BOL-303259-X Safety Extension Phase Following completion of the efficacy phase, all subjects were converted to BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label safety extension phase
IOP Reduction ≥ 25%	86 Participants	25 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Population: Safety population. Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population

Following assessments through 3 months (Visit 6), all participants, irrespective of previous randomization, converted to a single open label safety arm receiving BOL-303259-X QD in the evening for an additional 3 months through Visit 7. Adverse events were recorded throughout the comparative efficacy phase and open label extension phase.

Outcome measures

Measure	BOL-303259-X n=279 Participants BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye.	Timolol n=136 Participants Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye.	BOL-303259-X Safety Extension Phase n=384 Participants Following completion of the efficacy phase, all subjects were converted to BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label safety extension phase
Number of Participants With Ocular and Systemic Adverse Events >/= 1 nonocular AE	36 Participants	18 Participants	23 Participants
Number of Participants With Ocular and Systemic Adverse Events >/= 1 ocular (Study eye) AE	66 Participants	18 Participants	53 Participants

Adverse Events

BOL-303259-X

Serious events: 4 serious events

Other events: 50 other events

Deaths: 0 deaths

Timolol

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

BOL-303259-X Safety Extension Phase

Serious events: 2 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	BOL-303259-X n=279 participants at risk BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye during the efficacy phase	Timolol n=136 participants at risk Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye during the efficacy phase.	BOL-303259-X Safety Extension Phase n=384 participants at risk Following completion of the efficacy phase, all subjects were converted to BL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label extension phase
Injury, poisoning and procedural complications left shoulder subluxation of acromioclavicular joint	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Injury, poisoning and procedural complications Scapular fracture	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Injury, poisoning and procedural complications Fall	0.72% 2/279 • Number of events 2 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Cardiac disorders Coronary artery disease	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Vascular disorders Uncontrolled hypertension	0.00% 0/279 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.26% 1/384 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Cardiac disorders Chest pain	0.00% 0/279 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.26% 1/384 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Hepatobiliary disorders Cholelethiasis	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Injury, poisoning and procedural complications head injury	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Nervous system disorders Other convulsions	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Musculoskeletal and connective tissue disorders Pain in joint (shoulder)	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Nervous system disorders Subarachnoid hemorrhage	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Injury, poisoning and procedural complications Subdural hermorrhage	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Injury, poisoning and procedural complications Closed dislocation of finger	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Injury, poisoning and procedural complications Closed fracture of distal end of ulna	0.36% 1/279 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/136 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.00% 0/384 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.

Other adverse events

Measure	BOL-303259-X n=279 participants at risk BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months into the study eye during the efficacy phase	Timolol n=136 participants at risk Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months into study eye during the efficacy phase.	BOL-303259-X Safety Extension Phase n=384 participants at risk Following completion of the efficacy phase, all subjects were converted to BL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) for an additional 3 months during the open label extension phase
Eye disorders Conjunctival hyperemia	9.0% 25/279 • Number of events 32 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	0.74% 1/136 • Number of events 1 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	4.7% 18/384 • Number of events 19 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Eye disorders Eye irritation	7.2% 20/279 • Number of events 20 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	4.4% 6/136 • Number of events 7 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	2.1% 8/384 • Number of events 8 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.
Eye disorders Eye pain	5.7% 16/279 • Number of events 16 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	3.7% 5/136 • Number of events 6 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.	1.6% 6/384 • Number of events 7 • 6 months Safety Population (analyzed as treated). Of the subjects randomized, 415 instilled at least one dose of study medication and were included in the safety population. All subjects were converted to BOL-303259-X during the safety extension phase and AEs reported during that phase are presented below as a third arm.

Additional Information

H. DeCory, Director Medical Affairs

Bausch + Lomb, a division of Valeant Pharmaceuticals

Phone: 585 732-3284

Email: heleen_H_decory@bausch.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place